Arylsulfatase A deficiency

Arylsulfatase A deficiency
Description, Causes and Risk Factors:
Arylsulfatase A deficiency is a lysosomal storage disorder caused by the deficiency of arylsulfatase A, which leads to the intralysosomal accumulation of cerebroside sulfate. The incidence of this recessively inherited disease is estimated to be 1:40,000. The sulfatide storage affects mainly the central nervous system, causing a progressive demyelination that eventually leads to the death of the patient. Based on the age of onset three clinical variants of arylsulfatase A are differentiated: late infantile, juvenile, and adult.
Late-infantile. Onset is between ages one and two years. Typical presenting findings include weakness, hypotonia, clumsiness, frequent falls, toe walking, and slurred speech. Later signs include inability to stand, difficulty with speech, deterioration of mental function, increased muscle tone, pain in the arms and legs, generalized or partial seizures, compromised vision and hearing, and peripheral neuropathy. In the final stages children have tonic spasms, decerebrate posturing, and general unawareness of their surroundings.

Juvenile. Onset is between age four years and sexual maturity (age 12-14 years). Initial manifestations include decline in school performance and emergence of behavioral problems, followed by clumsiness, gait problems, slurred speech, incontinence, and bizarre behaviors. Seizures may occur. Progression is similar to but slower than the late-infantile form.

Adult. Onset occurs after sexual maturity, sometimes not until the fourth or fifth decade. Initial signs can include problems in school or job performance, personality changes, alcohol or drug abuse, poor money management, and emotional lability; in others, neurologic symptoms (weakness and loss of coordination progressing to spasticity and incontinence) or seizures predominate initially. Peripheral neuropathy is common. Disease course is variable, with periods of stability interspersed with periods of decline, and may extend over two to three decades. The final stage is similar to that for the earlier-onset forms.

The molecular basis for this heterogeneity is not known, and the determination of the residual arylsulfatase A activity does not permit differentiation between the various forms. Occasionally, the deficiency of arylsulfatase A is found in apparently healthy individuals, a condition known as arylsulfatase A pseudodeficiency. It has been shown that the arylsulfatase A synthesized in fibroblasts from individuals with arylsulfatase A pseudodeficiency is reduced in quantity and smaller in size when compared to normal. While the size difference has been attributed to altered glycosylation, the reasons for the attenuated arylsulfatase A activity remained unclear.
Symptoms:
Symptoms may include:
Difficulty with speech/slurred speech.

Diagnosis:
Arylsulfatase A deficiencyis suspected in individuals with progressive neurologic dysfunction and MRI evidence of a leukodystrophy. Arylsulfatase A deficiencyis suggested by arylsulfatase A (ARS-A) enzyme activity in leukocytes that is less than 10% of normal controls; however, assay of arylsulfatase A enzymatic activity cannot distinguish between arylsulfatase A deficiencyand arylsulfatase A pseudodeficiency, in which arylsulfatase A enzyme activity that is 5% to 20% of normal controls does not cause arylsulfatase A deficiency. Thus, the diagnosis of arylsulfatase A deficiencymust be confirmed by one or more of the following additional tests: molecular genetic testing of arylsulfatase A (the only gene in which mutation is known to cause arylsulfatase A deficiency), urinary excretion of sulfatides, and/or finding of metachromatic lipid deposits in nervous system tissue.
Treatment:
Treatment of seizures using antiepileptic drugs in standard protocols; treatment of contractures with muscle relaxants; physical therapy and an enriched environment to maximize intellect, neuromuscular function, and mobility; family support to enable parents and/or caregivers to anticipate decisions on walking aids, wheelchairs, feeding tubes, and other changing care needs.
Prevention of primary manifestations: Bone marrow transplantation (BMT), the only therapy for primary central nervous system manifestations, remains controversial because of its substantial risk and uncertain long-term effects. The best outcomes are observed when BMT is performed before symptoms occur.
Prevention of secondary complications: Physical therapy to prevent joint contractures; routine health care maintenance.
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.

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